EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families
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EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families. / Cheyssac, Claire; Dina, Christian; Leprêtre, Frédéric; Vasseur-Delannoy, Valérie; Dechaume, Aurélie; Lobbens, Stéphane; Balkau, Beverley; Ruiz, Juan; Charpentier, Guillaume; Pattou, François; Joly, Erik; Prentki, Marc; Hansen, Torben; Pedersen, Oluf; Vaxillaire, Martine; Froguel, Philippe.
In: Diabetes, Vol. 55, No. 4, 2006, p. 1171-6.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families
AU - Cheyssac, Claire
AU - Dina, Christian
AU - Leprêtre, Frédéric
AU - Vasseur-Delannoy, Valérie
AU - Dechaume, Aurélie
AU - Lobbens, Stéphane
AU - Balkau, Beverley
AU - Ruiz, Juan
AU - Charpentier, Guillaume
AU - Pattou, François
AU - Joly, Erik
AU - Prentki, Marc
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Vaxillaire, Martine
AU - Froguel, Philippe
PY - 2006
Y1 - 2006
N2 - One of the most replicated loci influencing type 2 diabetes-related quantitative traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2 diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P = 0.0001) was identified in a set of French families. To assess genetic variation underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a 3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1), and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148 families showed significant association of a frequent SNP, rs266714, located 2.47 kb upstream of EIF4A2, with familial type 2 diabetes (family-based association test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes linkage (genotype identical-by-descent sharing test, P = 0.02). However, no association was observed in three independent European diabetic cohorts. EIF4A2 controls specific mRNA translation and protein synthesis rate in pancreatic beta-cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its putative contribution to type 2 diabetes in the presence of metabolic stress will require further investigation.
AB - One of the most replicated loci influencing type 2 diabetes-related quantitative traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2 diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P = 0.0001) was identified in a set of French families. To assess genetic variation underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a 3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1), and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148 families showed significant association of a frequent SNP, rs266714, located 2.47 kb upstream of EIF4A2, with familial type 2 diabetes (family-based association test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes linkage (genotype identical-by-descent sharing test, P = 0.02). However, no association was observed in three independent European diabetic cohorts. EIF4A2 controls specific mRNA translation and protein synthesis rate in pancreatic beta-cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its putative contribution to type 2 diabetes in the presence of metabolic stress will require further investigation.
KW - Age of Onset
KW - Chromosome Mapping
KW - Chromosomes, Human, Pair 3
KW - Diabetes Mellitus, Type 2
KW - Eukaryotic Initiation Factor-4A
KW - Female
KW - France
KW - Genes, Dominant
KW - Genes, Recessive
KW - Humans
KW - Kininogens
KW - Male
KW - Nuclear Family
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait Loci
KW - Sex Ratio
M3 - Journal article
C2 - 16567544
VL - 55
SP - 1171
EP - 1176
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 4
ER -
ID: 38455522